We have recently developed a quantitative description of the endplate conductance increase from a model which assumes rapid binding of acetylcholine to its receptor followed by a rate limiting conformational change that is responsible for opening endplate channels. This analysis of postjunctional mechanisms is to be continued by two projects. (1) Little information is currently available about the binding step which precedes the hypothesized gating molecule conformational change. To study this binding mechanism, we wish to determine the relation between endplate conductance and concentration of cholinergic ligands. Conductance increases in voltage clamped endplates, visualized with Nomarski optics, are to be produced by iontophoretic application of carbachol, ACh and other ligands, and the ligand concentration is to be measured by a newly developed ion exchange microelectrode that is selectively sensitive to these drugs. The observed dose-response curve is to be interpreted in terms of possible binding mechanisms. (2) In order to detect more directly the conformational change thought to underlie postjunctional conductance increases, we propose to make simultaneous optical and electrical measurements on visualized endplates to which ACh and other ligands have been applied. Changes in light scattering, birefringence, refractive index, absorption, and extrinsic fluorescence (using various fluorescent probes) will be sought. Our goal will be to interpret optical properties which covary with conductance in terms of molecular mechanisms responsible for the endplate conductance increase.